anastrozole / Generic mfg. - LARVOL DELTA

NATALEE update: Safety and treatment (tx) duration of ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2− early breast cancer (EBC) (ESMO-BC 2024) - "Methods Pts in NATALEE were randomized 1:1 to RIB (400 mg/d 3 wk on/1 wk off, 36 mo) + NSAI (letrozole or anastrozole, ≥60 mo) or NSAI alone. Men and premenopausal women also received goserelin...Table: 113MO Most common AEs (>10% in RIB + NSAI arm in the safety set) AEs, n (%) RIB + NSAI n = 2525 NSAI alone n = 2442 Neutropeniaa 1579 (62.5) 113 (4.6) Infectionsa 1253 (49.6) 883 (36.2) Arthralgia 942 (37.3) 1058 (43.3) Hepatobiliary toxicitya,b 667 (26.4) 273 (11.2) Leukopeniaa 595 (23.6) 111 (4.5) Nausea 588 (23.3) 190 (7.8) Headache 575 (22.8) 415 (17.0) Fatigue 564 (22.3) 322 (13.2) Hot flush 486 (19.2) 489 (20.0) Asthenia 428 (17.0) 291 (11.9) Alopecia 380 (15.0) 109 (4.5) Diarrhea 366 (14.5) 135 (5.5) Constipation 335 (13.3) 123 (5.0) Cough 332 (13.1) 201 (8.2) Insomnia 292 (11.6) 281 (11.5) Pyrexia 280 (11.1) 147 (6.0) Back pain 272 (10.8) 247 (10.1) Pain in extremity 261 (10.3) 219 (9.0) aGrouped term per MedDRA v. 26.0bAST, ALT, ALP, bilirubin, and GGTP..."

Clinical • Alopecia • Back Pain • Breast Cancer • CNS Disorders • Constipation • Cough • Fatigue • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hepatology • HER2 Positive Breast Cancer • Immunology • Infectious Disease • Insomnia • Leukopenia • Musculoskeletal Pain • Neutropenia • Oncology • Pain • Respiratory Diseases • Sleep Disorder • Solid Tumor • HER-2

Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial. (ASCO 2025) - P3 | " Pts with HR+/HER2– ABC who had received ≥6 months of 1L AI (anastrozole/letrozole) + CDK4/6i (abemaciclib/palbociclib/ribociclib) were enrolled and had ctDNA tested for ESR1m every 2–3 months, coinciding with routine imaging. Camizestrant + CDK4/6i guided by emergence of ESR1m during 1L AI + CDK4/6i in pts with HR+/HER2– ABC resulted in a statistically significant and clinically meaningful improvement in PFS. SERENA-6 is the first global Phase 3 trial to demonstrate clinical utility of using ctDNA to detect and treat emerging resistance, ahead of disease progression. These findings represent a potential new treatment strategy to optimize and improve 1L patient outcomes."

Circulating tumor DNA • Clinical • Late-breaking abstract • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Adjuvant ribociclib (RIB) plus nonsteroidal aromatase inhibitor (NSAI) in patients (pts) with HR+/HER2− early breast cancer (EBC): NATALEE 5-year outcomes (ESMO 2025) - "Methods Pts with HR+/HER2− EBC were randomized 1:1 to RIB (400 mg/d; 3 weeks on/1 week off for 3 y) + NSAI (letrozole 2.5 mg/d or anastrozole 1 mg/d for 5 y) or NSAI alone. Men and premenopausal women received goserelin...Conclusions In this 5-year landmark analysis with mature efficacy data, RIB + NSAI reduced the risk of invasive and distant disease recurrence compared with NSAI alone, including in pts with high-risk N0 disease. A positive trend for OS in favor of RIB + NSAI continues to emerge."

Clinical • Late-breaking abstract • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Giredestrant vs standard-of-care endocrine therapy as adjuvant treatment for patients with estrogen receptor-positive, HER2-negative early breast cancer: Results from the global Phase III lidERA Breast Cancer trial (SABCS 2025) - P3 | "Giredestrant, a next-generation oral selective estrogen receptor antagonist and degrader (SERD), was shown to be more potent than other SERDs (Liang 2021; Bardia 2023) and demonstrated superior antiproliferative activity vs anastrozole in the neoadj coopERA BC trial (Hurvitz 2023)... Pts with Stage I-III ER+ HER2- eBC were randomized 1:1 to giredestrant 30 mg oral daily (with an LHRH agonist in pre- and peri-menopausal women, and men) or standard-of-care ET (tamoxifen or aromatase inhibitor) for 5 years (yr)... lidERA BC is the first Phase III trial to demonstrate benefit with an oral SERD in eBC. Giredestrant tx resulted in a statistically significant and clinically meaningful IDFS improvement vs standard-of-care ET in ER+, HER2- eBC. OS trended in favor of the giredestrant arm, and DRFI was improved vs standard-of-care ET."

Clinical • P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Surgical outcomes in the ALTERNATE trial (Alliance A011106) -a randomized phase 3 neoadjuvant endocrine therapy (NET) trial in postmenopausal women with clinical stage II/III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) (SABCS 2025) - P3 | "In this analysis we assess the surgeons' approach in the context of NET. The ALTERNATE trial is a phase III study that randomized postmenopausal patients (pts) with clinical stage II/III ER+ HER2- BC to receive neoadjuvant anastrozole (A), fulvestrant (F), or both for 6 mos. With NET, 69.9% of pts achieved BCS, including 43.8% deemed ineligible pre-NET. Given the low rate of pCR to NET, there should not be the expectation of pCR in +LNs. Based on the procedures performed in pts with +SLNs, it appears that surgeons were applying ACOSOG Z0011 criteria for pts having BCS, but were less likely to omit ALND for +LN in pts having mastectomy."

Clinical • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Adjuvant ribociclib plus nonsteroidal aromatase inhibitor therapy in patients with HR-positive/HER2-negative early breast cancer: 5-year follow-up of NATALEE efficacy outcomes and updated overall survival. (PubMed, ESMO Open) - "This prespecified 5-year follow-up of efficacy outcomes from NATALEE demonstrated that ribociclib + NSAI continued to reduce the risk of recurrence beyond the 3-year treatment window, supporting its use as adjuvant therapy in patients with HR-positive/HER2-negative EBC. An ongoing positive trend for improved OS in favor of ribociclib + NSAI was observed."

Clinical • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Cost-Effectiveness Analysis of Hormone Therapy for Breast Cancer in Japan. (PubMed, Asia Pac J Clin Oncol) - "Anastrozole was less cost-effective than tamoxifen in Japan. Our findings support clinical practice and suggest that payers and policymakers should promote cost-effective therapies."

Clinical • HEOR • Journal • Breast Cancer • Musculoskeletal Diseases • Oncology • Solid Tumor

Treatment of ER-positive breast cancer with FDA-approved aromatase inhibitors. (PubMed, Cancer Treat Res Commun) - "The current FDA-approved SERMs include tamoxifen, toremifene, and raloxifene, while the only SERD that has been approved to date is fulvestrant. Various generations of AIs are available for the treatment of hormone-positive breast cancers, including exemestane, letrozole, and anastrozole. Aromatase inhibitors are often utilized following relapse with therapies such as tamoxifen. Herein, we focus on and review the major FDA-approved aromatase inhibitors used to treat ER-positive breast cancer."

FDA event • Journal • Review • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER

Postoperative Adjuvant Anastrozole for 10 or 5 Years in Patients With Hormone Receptor-Positive Breast Cancer: AERAS, a Randomized Multicenter Open-Label Phase III Trial. (PubMed, J Clin Oncol) - "Continuing adjuvant anastrozole for an additional 5 years after 5 years of initial treatment with anastrozole or tamoxifen followed by anastrozole was well tolerated and improved DFS. Although no difference in overall survival was observed as in other trials, extended anastrozole therapy could be one treatment choice in postmenopausal patients with hormone receptor-positive breast cancer."

Journal • P3 data • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Updated results and an exploratory analysis of ESR1m circulating tumor DNA (ctDNA) dynamics from SERENA-6, a phase 3 trial of camizestrant (CAMI) + CDK4/6 inhibitor (CDK4/6i) for emergent ESR1 mutations (ESR1m) during first-line (1L) endocrine-based therapy and ahead of disease progression in patients (pts) with HR+/HER2- advanced breast cancer (ABC) (SABCS 2025) - "Methods SERENA-6, a randomized, double-blind, phase 3 trial, enrolled pts with HR+/HER2- ABC who had received ≥6 months of 1L AI (anastrozole/letrozole) + CDK4/6i (palbociclib/ribociclib/abemaciclib). No new safety signals were observed. These results further support an early switch to CAMI + CDK4/6i during 1L therapy to delay disease progression."

Circulating tumor DNA • Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Hepatic steatosis and fibrosis are associated with metabolic factors rather than endocrine therapy in breast cancer patients. (PubMed, Transl Gastroenterol Hepatol) - "Patients were divided into four groups: no hormone therapy (n=55, 32.2%), tamoxifen only (n=72, 42.1%), anastrozole only (n=16, 9.4%), and both drugs (n=28, 16.4%). Metabolic factors were independently associated with SLD development and progression, regardless of hormone therapy exposure. Patients in continuous use of endocrine therapy had no dynamic changes in liver stiffness after 24 months of follow-up."

Journal • Breast Cancer • Cardiovascular • Diabetes • Dyslipidemia • Fibrosis • Genetic Disorders • Hepatology • Hypertension • Immunology • Liver Cirrhosis • Metabolic Disorders • Obesity • Oncology • Solid Tumor

Testing Whether Hormone Therapy With Ribociclib is as Effective as Chemotherapy Followed by Hormone Therapy With Ribociclib for the Treatment of High Anatomic Stage Breast Cancer With Low Recurrence Risk, The RxFINE-Low Trial (clinicaltrials.gov) - P3 | N=1978 | Not yet recruiting | Sponsor: National Cancer Institute (NCI)

New P3 trial • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

SEVERE SHORT STATURE IN AN ADOLESCENT MALE WITH LARON SYNDROME DUE TO A NOVEL GHR VARIANT: INITIAL RESPONSE TO RECOMBINANT IGF-1 AND AROMATASE-INHIBITOR TREATMENT (WRMC 2026) - "An aromatase-inhibitor was added (initially letrozole, then anastrozole due to high T) to delay epiphyseal fusion and augment growth potential. This unique case of severe LS involves a novel homozygous missense variant in the GHR affecting the EC GH binding domain and highlights the potential of meaningful linear growth in response to combined rhIGF-1 and aromatase-inhibitor treatment. Further follow-up is needed to evaluate the full effect of treatment on adult height. The presence of normal GHBP is unusual in LS but has rarely been seen in GHR variants involving EC binding domain."

Genetic Disorders • Hypoglycemia • Metabolic Disorders • Obesity • IGF1 • IGFBP3

Dalpiciclib plus letrozole or anastrozole as first-line treatment for HR+/HER2- advanced breast cancer (DAWNA-2): A phase III trial (ESMO 2022) - P3 | "Clinical trial identification NCT03966898. Conclusions Adding dalp to letrozole/anastrozole significantly prolonged PFS in HR+/HER2- ABC, with manageable toxicities. Dalp is the 4 th CDK4/6 inhibitor showing survival benefit with letrozole or anastrozole in untreated HR+/HER2- ABC, or with fulvestrant in pretreated HR+/HER2- ABC, in addition to palbociclib, ribociclib and abemaciclib."

Clinical • Late-breaking abstract • P3 data • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2

Neoadjuvant nivolumab (NIVO) + palbociclib (PALBO) + anastrozole (ANA) for estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2_) primary breast cancer (BC): CheckMate 7A8 (ESMO-BC 2022) - P2 | "Neoadjuvant NIVO + PALBO + ANA showed a higher incidence of grade ≥3 hepatic TRAEs than historical single-agent safety profiles. These findings show a potential safety risk for the use of endocrine therapy with PD-1 + CDK 4/6 blockade."

Clinical • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • ER • HER-2

IMPULSE: Implementation Study to Describe and Compare Retention Rate and Adherence to Adjuvant Therapy With Ribociclib With and Without Usage of Mobile Application in Patients With HR+ HER2-negative Stage II and III Breast Cancer in Real-world Practice (clinicaltrials.gov) - P=N/A | N=240 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting | Trial completion date: Jul 2029 ➔ Dec 2029 | Initiation date: Jul 2025 ➔ Jan 2026 | Trial primary completion date: Jul 2029 ➔ Dec 2029

Enrollment open • Real-world evidence • Trial completion date • Trial initiation date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

TACTIVE-N: Phase 2 study of neoadjuvant vepdegestrant, a PROteolysis TArgeting chimera (PROTAC) estrogen receptor (ER) degrader, or anastrozole in postmenopausal ER+/human epidermal growth factor receptor 2 (HER2)- localized breast cancer (BC) (ESMO 2025) - P2 | "Conclusions Neoadjuvant vepdegestrant was well tolerated and demonstrated biological and clinical activity in postmenopausal women with ER+/HER2- localized BC. Vepdegestrant led to robust ER protein degradation in tumor tissue, supporting its pharmacodynamic effect in pts with BC."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

A Phase II Adjuvant Trial Evaluating the Impact of Omitting Chemotherapy Based on Patient's Selection for Moderate to High-Anatomical Risk, Low-Genomic Risk, ER-positive, HER2-negative Breast Cancer with a Combination Regimen of Ribociclib and Optimized Endocrine Therapy - SELECT Trial (SABCS 2025) - P2 | "Optimized ET includes an oral aromatase inhibitor (letrozole or anastrozole) for all participants, with the addition of a GnRH agonist (goserelin) to achieve gonadal suppression in all men and premenopausal women. Recruitment is ongoing. Clinical trial information: NCT06953882."

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

MONARCH plus: A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer (clinicaltrials.gov) - P3 | N=463 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Jan 2027 ➔ Mar 2028

Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

A Study of LY2835219 (Abemaciclib) in Combination With Therapies for Breast Cancer That Has Spread (clinicaltrials.gov) - P1 | N=198 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • CDK6 • HER-2

SERENA-1: Study of AZD9833 Alone or in Combination in Women With Advanced Breast Cancer. (clinicaltrials.gov) - P1 | N=396 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2026 ➔ Jun 2027

First-in-human • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

MONARCH 3: A Study of Nonsteroidal Aromatase Inhibitors Plus Abemaciclib (LY2835219) in Postmenopausal Women With Breast Cancer (clinicaltrials.gov) - P3 | N=493 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

KEYNOTE 287: A Study of Abemaciclib (LY2835219) in Participants With Non-Small Cell Lung Cancer or Breast Cancer (clinicaltrials.gov) - P1 | N=100 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • KRAS • PD-L1

The prognostic and predictive value of the luminal-like subtype in hormone receptor-positive breast cancer: an analysis of the DATA trial. (PubMed, ESMO Open) - P3 | "In patients with hormone receptor-positive breast cancer, the luminal B-like subtype was associated with a significantly worse prognosis when compared with the luminal A-like subtype. Extended anastrozole therapy halved the risk of DR and BCSM in patients with luminal A-like tumours, whereas no effect was seen in patients with luminal B-like tumours."

Journal • Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Testing Low Dose Tamoxifen for Invasive Breast Cancer, the (LoTam) Trial (clinicaltrials.gov) - P3 | N=1156 | Suspended | Sponsor: Alliance for Clinical Trials in Oncology | Recruiting ➔ Suspended

Trial suspension • Breast Cancer • Endometrial Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2